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Background: Origanum vulgare is used in traditional medicine for antimicrobial, anti-inflammatory and antioxidant activities. Objectives: The present study was designed to investigate the protective effects of O. vulgare leaves extract on experimentally induced intestinal ischemia/reperfusion (I/R) injury in rats. Materials and Methods:In this experimental study, 24 male Wistar albino rats randomly divided into four groups. Group I/R underwent ischemia-reperfusion of the intestine (45 minutes of ischemia followed by 1 hour of reperfusion). Treatment groups I and II were given O. vulgare extract (200 and 400 ppm) via oral gavages for 1 week before inducing I/R. Group sham was given normal saline orally without inducing I/R. After the experiments, the jejunum was removed and the tissues were processed for histomorphometric examination of mucosa. Results: The treatment with O. vulgare extract significantly decreased mucosal damages in the treatment groups compared to group I/R, while severe mucosal damages were observed in the group I/R. Also, there was significant difference between treatment groups I and II (P = 0.054). Group sham observed normal intestinal mucosa. Conclusions: According to the results of current study, administration of O. vulgare extract protects the intestinal mucosa from I/R injuries.